TACI Expression and Signaling in Chronic Lymphocytic Leukemia

Mamara, Antigoni; Germenis, Anastasios E.; Kompoti, Maria; Palassopoulou, Maria; Μανδαλά, Ευδοκία; Banti, Anastasia; Giannakoulas, Nikolaos; Speletas, Matthaios

doi:10.1155/2015/478753

Cited by 9 publications

(14 citation statements)

References 45 publications

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“…There are several studies which investigate the prognostic role of these molecules in hematological malignancies, particularly in CLL. In a study by Mamara et al [28], BAFF and TACI levels were found to be lower in 94 CLL patients, however a significant association with clinical or laboratory risk factors was not demonstrated in concordance with our results. Similar results were reported in two studies by Planelles et al and Haiat et al [30,31].…”

Section: Discussionsupporting

confidence: 65%

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Prognostic Significance of Serum BAFF, APRIL, TACI and BCMA Levels in Chronic Lymphocytic Leukemia

Menteşe

Yeğin

Gökçen

et al. 2018

Indian J Hematol Blood Transfus

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As chronic lymphocytic leukemia (CLL) has a variable disease course, novel prognostic markers and risk assessment models are being developed in order to identify high-risk patients who may need early treatment. The two tumor necrosis factor family proteins BAFF and APRIL and their receptors BAFF-R, TACI and BCMA are considered to play a critical role in the survival of normal B cells. In order to highlight the pathophysiological role of this complicated biological network, we aimed to analyze the potential prognostic effects of BAFF, APRIL, TACI and BCMA in CLL patients. We investigated the prognostic impact of serum BCMA, TACI, BAFF and APRIL levels in 129 newly diagnosed CLL patients [median age: 64 (39-88) years; male/female: 85/44]. Serum BAFF, TACI and BCMA levels were significantly lower in the patient group compared to the control group (p \ 0.001), while serum APRIL level did not differ significantly between two groups (p [ 0.05). Serum BCMA [(p = 0.029; r = 0.208)] and TACI levels [(p = 0.011; r = 0.241)] were positively correlated with serum free light chain ratio. Serum BAFF [(p = 0.008; r =-0.236)] and BCMA [(p = 0.042; r =-0.183)] levels were negatively correlated with Rai stage. Overall survival (OS) was relatively better in patients with low serum BAFF levels [60 (1-187) months vs 39.5 (0-256) months; p = 0.063]. Probability of OS was higher in patients with low BAFF levels when compared to patients with normal levels, without statistical significance (53.6% vs 23.6%; p [ 0.05). Large prospective studies are needed to validate the prognostic role of this essential biological pathway in CLL.

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Section: Discussionsupporting

confidence: 65%

“…In order to highlight the pathophysiological role of this complicated biological network, we aimed to analyze the potential prognostic effects of BAFF, APRIL, TACI and BCMA in CLL patients [16,18,[28][29][30][31][32][33][34][35][36]. Table 2).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Serum BAFF, APRIL, TACI and BCMA Levels in Chronic Lymphocytic Leukemia

Menteşe

Yeğin

Gökçen

et al. 2018

Indian J Hematol Blood Transfus

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“…Some studies indicated that high TACI expression improves the survival ability of CLL cells by protecting them from apoptosis in vitro [ 18 , 19 ], which in consequence may worsen the clinical course of the disease. Therefore, we decided to make additional analysis, and check whether we will be able to notice relationship between high TACI expression and Rai stage (Rai Staging System).…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, the APRIL-TACI interaction has been shown to be pivotal to a class switch recombination (CSR) to IgA [ 11 ]. Additionally, some studies indicated that a high TACI expression improves the survival ability of CLL cells protecting them from apoptosis in vitro [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Association of Common Variants of TNFSF13 and TNFRSF13B Genes with CLL Risk and Clinical Picture, as Well as Expression of Their Products—APRIL and TACI Molecules

Jasek

Bojarska‐Junak

Sobczyński

et al. 2020

Cancers

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Interactions between APRIL (TNFSF13) and its receptor TACI (TNFRSF13B) are implicated in providing survival benefits for chronic lymphocytic leukaemia (CLL) cells. Here we explored the relationship between TNFSF13 and TNFRSF13B SNPs and expression of APRIL and TACI molecules and performed extended case-control study to evaluate earlier observations. Expression of APRIL and TACI was detected by FACS for 72 and 145 patients, respectively, and soluble APRIL was measured by ELISA in plasma of 122 patients. Genotypes were determined in 439 CLL patients and 477 control subjects with TaqMan Assays or restriction fragment length polymorphism (RFLP). The rs4968210GG genotype of TNFSF13 was associated with a lower percentage of CD19+APRIL+ cells in CLL patients when compared to (AA + GA) genotypes (p-value = 0.027). Homozygosity at rs11078355 TNFRSF13B was associated with higher CD19+ TACI+ cell percentage in CLL patients (p-value = 0.036). The analysis of extended groups of patients and healthy controls confirmed the association of TNFSF13 rs3803800AA genotype with a higher CLL risk (OR = 2.13; CI95% = 1.21; 3.75; p-value = 0.007), while the possession of TNFRSF13B rs4985726G allele (CG + GG) genotype was associated with lower risk of CLL (OR = 0.69; CI95% = 0.51; 0.95; p-value = 0.02). Genetic variants of TNFSF13 and TNFRSF13B may have an impact on APRIL and TACI expression and may be considered as possible CLL risk factors.

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“…cDNA was prepared from total RNA from mononuclear cells as described (26, 27). Expression of TACI and BAFFR was determined by quantitative Real-Time RT-PCR, while the expression of BCMA, APRIL, BAFF , and deltaBAFF (Δ BAFF ) transcripts was determined by semi-quantitative conventional RT-PCR using beta-2-microglobulin (B2M) transcripts as reference (Supplementary Methods).…”

Section: Methodsmentioning

confidence: 99%

BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner

et al. 2019

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BAFF, APRIL and their receptors regulate the survival, maturation and homeostasis of mature B-cells. Despite the lack of a functional role of BAFF/APRIL system during normal early B-cell development, previous studies indicated a contribution of these molecules in the pathogenesis of B-lineage acute lymphoblastic leukemia (B-ALL). Here, we evaluated the expression of this system in B-ALL and its involvement in spontaneous and drug-induced apoptosis of B-lymphoblasts, taking into consideration the distinct disease subtypes. We found that BAFFR is the most predominant aberrantly expressed receptor in B-ALL and that its expression, along with BCMA and APRIL, positively correlates with the maturation stage of B-lymphoblasts. Moreover, the binding of the E2A-PBX1 chimeric protein to the BAFFR promoter suggests that the transcriptional activator promotes the increase in BAFFR expression observed in about 50% of pre-B-ALL patients carrying the t (1, 19) translocation. BAFF binding to BAFFR led to the processing of NF-κB2 p100 in pre-B ALL cells suggesting that BAFFR can activate the NF-κB2 pathway in pre-B ALL cells. Surprisingly, we found that BAFF treatment promotes the cell death of primary BCR-ABL + BAFFR + pre-B-lymphoblasts in adult B-ALL. It also enhances glucocorticoid-induced apoptosis in the E2A-PBX1 + pre-B-ALL cell line 697. These data suggest that BAFF/BAFFR signaling in B-ALL cells differs from normal B cells and that it may affect the pathogenesis of the disease.

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TACI Expression and Signaling in Chronic Lymphocytic Leukemia

Cited by 9 publications

References 45 publications

Prognostic Significance of Serum BAFF, APRIL, TACI and BCMA Levels in Chronic Lymphocytic Leukemia

Prognostic Significance of Serum BAFF, APRIL, TACI and BCMA Levels in Chronic Lymphocytic Leukemia

Association of Common Variants of TNFSF13 and TNFRSF13B Genes with CLL Risk and Clinical Picture, as Well as Expression of Their Products—APRIL and TACI Molecules

BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner

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